This Program is based on two pivotal findings by Program members on the origin and nature of cancer stem cells. The first discovery is that only a small percentage of the cancer cells, the stem cells, drive the growth and metastasis of tumors. These cells must be eliminated if the patient is to be cured. Second, cancers arise because of unregulated self-renewal, the process by which normal and neoplastic stem cells generate new cells at the same developmental stage. As self-renewal is a critical function of both cancer stem cells and their normal counterparts, approaches must be found to characterize and differentiate these self-renewal pathways in order to make cancer stem cells tractable therapeutic targets. The identification of the first cancer stem cells and validation of the cancer stem cell hypothesis both demand and facilitate the integration of basic research and clinical studies. This Program intends to use the Cancer Center mechanism to facilitate the integration of these important insights into cancer biology with the clinical expertise necessary to translate them to the advancement of cancer treatment. To accomplish this objective, we have assembled a large team of leading basic and clinical researchers to work together to address the following Program objectives: 1) To investigate potential pathways critical for the self renewal, spread and survival of cancer stem cells 2) To develop new therapies directed against cancer stem cells